tbuckley/cabot-search huggingface dataset:
Neoadjuvant chemoradiation in elderly Irish patients with esophageal cancer: A review of the clinical outcomes and toxicity.
Authors: Ronan Andrew Mc Laughlin, Majid Almeraikhi, Humaid Alkaabi, Fianait Bligh, Christopher Cluxton, David Mcmahon, Orla Fitzpatrick, Michael R Conroy, Bryan T. Hennessy, Brian O'Neill, Jarushka Naidoo, Oscar S. Breathnach, William Grogan, Adrian Gerard Murphy, Patrick G. Morris
Journal: Journal of Clinical Oncology (2023)

335 Background: In locally advanced esophageal cancer, neoadjuvant chemo-radiotherapy improves survival compared with surgery alone. In the Chemo-Radiotherapy for Oesophageal cancer followed by Surgery Study (CROSS), the median age was 60. However, 1/3 of patients diagnosed with esophageal cancer are over 70 years. The CROSS outcomes are therefore limited in its application to older patients. The objective of this study is to report and compare the outcomes and tolerability in elderly patients (≥70 years), who underwent neoadjuvant chemo-radiation for esophageal cancer with younger patients &lt; 70 years. Methods: A retrospective analysis of patients treated with neoadjuvant chemo-radiation for esophageal cancer between 1 st January 2015 and 1 st January 2021 was completed. Baseline characteristics and haematological toxicities were reported. Pathological response was reported. Survival was estimated using the Kaplan-Meier method. Results: In total 105 patients were included; 35 (33%) were ≥ 70 years and 70 (67%) patients were &lt; 70 years. In the elderly cohort, the median age was 75 (70-86) and the younger cohort median age was 60 (29-69). 73% of patients in each cohort were male. 31 (89%) of older adults experienced any grade of anaemia compared with 45 (64%) of the younger cohort. Only one patient experienced ≥ grade 3 anaemia in each cohort. 18(51%) and 33(47%) of older and younger patients respectively experienced any grade of neutropenia. 5(14%) older and 7(10%) younger patients experienced ≥ grade 3 neutropenia. 15(43%) and 43(61%) of older and younger patients experienced any grade of thrombocytopenia. No patients experienced ≥ grade 3 thrombocytopenia. 80% of the older and 86% of the younger cohort proceeded to surgery. 3(11%) and 17(29%) of the older and younger cohorts respectively who underwent surgery achieved a complete pathological response. There was no difference in overall survival (OS) between the cohorts (p=0.48). There was also no difference in progression free survival (PFS) between the cohorts. Conclusions: In conclusion, we confirm that neoadjuvant chemo-radiation is tolerable in patients ≥ 70 when compared with patients &lt; 70 years. Both OS and PFS is similar in both cohorts. We recommend the use of neoadjuvant therapy in appropriately selected patients ≥ 70 years.
Penpulimab plus chemotherapy with or without anlotinib as first-line treatment for patients with advanced esophageal squamous cell carcinoma (ANSWER): A randomized, two-arm, clinical trial in progress.
Authors: Wei Wang, Shuimiao Lin, Rong Wang, Dehua Wu
Journal: Journal of Clinical Oncology (2023)

TPS482 Background: For patients with advanced esophageal squamous cell carcinoma (ESCC), the combination of immune checkpoint inhibitors with chemotherapy has demonstrated synergistic antitumor activity and manageable safety profile. Anti-angiogenic targeted drugs for ESCC patients are still being explored. Penpulimab is a humanized high-affinity IgG1 anti-programmed cell death 1 (PD-1) monoclonal antibody engineered to completely eliminate Fcγ receptor binding and Fc-mediated effector functions that can compromise antitumor activity. Anlotinib, an oral small molecule tyrosine kinases inhibitor, targeting VEGFR 1/2/3, FGFR 1-4, PDGFR α/β and c-kit, have been recommended by the guidelines for advanced ESCC in China because of its good efficacy and tolerance. The purpose of the study was to investigate the efficacy and safety of penpulimab plus chemotherapy with or without anlotinib as first-line treatment for patients with advanced ESCC. Methods: This is a multi-center, two-arm, phase II study which enrolled patients with advanced ESCC. Eligible patients are aged 18-75 years, ECOG performance status 0~1. Approximately 100 patients will be randomly assigned 1:1 to induction with penpulimab (200mg, iv, d1, q3w) plus chemotherapy (TP: cisplatin [60-75mg/m 2 , iv, d1-d3, q3w] plus paclitaxel [135-175mg/m 2 , iv, d1, q3w] or albumin-bound paclitaxel [200-260mg/m 2 , iv, d1, q3w]) for 4-6 cycles followed by consolidation with penpulimab (200mg, iv, d1, q3w) (arm 1) or induction with penpulimab (200mg, iv, d1, q3w) plus anlotinib (10mg/d [&lt;60kg] / 12mg/d [≥60kg], p.o., d1~14, q3w) plus chemotherapy (TP: cisplatin [60-75mg/m2, iv, d1-d3, q3w] plus paclitaxel [135-175mg/m2, iv, d1, q3w] or albumin-bound paclitaxel [200-260mg/m2, iv, d1, q3w]) for 4-6 cycles followed by consolidation with penpulimab (200mg, iv, d1, q3w) and anlotinib (10mg/d [&lt;60kg)/12mg/d [≥60kg], p.o., d1~14, q3w) (arm 2). Randomization will be stratified by gender (male or female), age (&lt;65, &gt;65), PD-L1 combined positive score (CPS; &lt;1, ≥1, ≥5, ≥10), metastatic site, history of surgery and disease. Patients in arm 1 were treated with second-line anlotinib combined with penpulimab after progression until further disease progression. Patients in arm 2 will continue treated with first-line anlotinib combined with penpulimab until disease progression. Tumor imaging assessment will be performed q6w for 1-6 cycle and q9w thereafter. The primary endpoint was objective response rate (per RECIST v1.1 assessed by investigator). Secondary endpoints included disease control rate, progression-free survival (per RECIST v1.1 assessed by investigator), overall survival, safety and quality of life score. Enrollment in this trial is ongoing. Clinical trial information: NCT05214222 .
Trial in progress: A phase 2 study of CTX-009 in adult patients with metastatic colorectal cancer who have received two or three prior systemic chemotherapy regimens.
Authors: Marilyn Fontaine, Sarah Pilgrim, Thomas Schuetz
Journal: Journal of Clinical Oncology (2023)

TPS281 Background: CTX-009 is a recombinant bispecific antibody that binds both delta-like ligand-4 (DLL4) and vascular endothelial growth factor A (VEGF-A). The antibody simultaneously inhibits the DLL4-Notch 1 and VEGF A-VEGF receptor signaling pathways. Patients with unresectable locally advanced and unresectable metastatic colorectal cancer (CRC) are sequentially treated with various combinations or single agent courses of cytotoxic chemotherapy agents including 5-fluorouracil and its orally administered family members (capecitabine, TAS-102) oxaliplatin, and irinotecan, as well with targeted therapies such as bevacizumab or aflibercept (anti-VEGF), cetuximab or panitumumab (anti-EGFR), or multitargeted tyrosine kinase inhibitors (regorafenib). In subsets of patients who have had multigene panel testing done and whose tumors have been identified as having mutations that drive their disease such as defective mismatch repair, HER-2 overexpression, or NTRK fusions specific treatments with respectively PD-1 or PD-L1 inhibitors, traztuzumab or larotrectinib or entrectinib can also be used effectively. Despite the approval of multiple new agents in the past two decades, the goals of therapy are generally palliative although some patients will have long disease-free intervals when they respond to therapy. In the cases of patients whose disease has progressed, or who have not tolerated 2 or 3 prior lines of therapy, the expectation for tumor response with the available treatments are less than 5% and the median overall survival is approximately 6 months (for 3rd line therapy) or less (for 4th line therapy). In a Phase 1 study with CTX-009, responses have been seen in patients with colorectal cancers who were treated in the 4th line setting. Since CTX-009 targets tumor induced neoangiogenesis, and monoclonal antibodies that target vascular endothelial growth factor (VEGF) has been shown to extend the lives of patients with advanced colorectal cancer, testing of CTX-009 in the setting of advanced treatment refractory colorectal cancer is justified. Methods: CTX-009 is being evaluated in an open label study in patients with previously treated metastatic CRC. This study is designed as an adaptive Simon Two Stage study, with approximately 37 patients to be enrolled into Stage 1. If criteria are met to move to Stage 2, an additional 47 patients will be enrolled, for a total of approximately 84 patients. To move to stage 2 of the study, 3 or more Complete or Partial Responses must be confirmed via RECIST 1.1. Patients will be treated in 28-day cycles, with CTX-009 administration on Day 1 and 15. The primary objective of the study is to assess the efficacy of CTX-009, as measured by Overall Response Rate (ORR). The study is currently activating sites with first patient in expected in 2022. Clinical trial information: NCT05513742 .
Clinical outcomes of endoscopic resection of gastric GIST.
Authors: Jong-Jae Park, Moon Kyung Joo, Beom Jae Lee, Sunsuk Kim, Hoon Jai Chun
Journal: Journal of Clinical Oncology (2023)

383 Background: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in stomach. We evaluated the long-term clinical outcomes of endoscopic treatment for gastric GISTs. Methods: This is a retrospective study that enrolled 135 cases of gastric subepithelial tumors (SETs) resected by endoscopic procedures and confirmed as GISTs by histopathology from 2005 to 2019. The immediate and long-term clinical outcomes were analyzed retrospectively. Results: The mean age was 57.9 years, and the mean tumor size was 2.1 cm. Of the tumors, 43.0% were located in the corpus, followed by the fundus (26.7%) and cardia (17.0%). Most tumors (85.2%) were resected by endoscopic submucosal dissection. Macroperforation occurred in 4.4% and microperforation in 6.7% of the cases. The R0 resection rate was 15.6%. However, complete resection by the endoscopic view was 90.4%, of which 54.8% were in the very-low-risk group, followed by the low (28.1%), intermediate (11.9%), and high-risk groups (5.2%). During 36.5 months of follow-up, recurrence was found in four (3.4%) of the 118 patients who were monitored for more than six months (low risk group:1/37, 2.7%; intermediate risk group: 2/11, 18.2%; high risk group: 1/6, 16.7%). Conclusions: Endoscopic treatment of a GIST appears to be a feasible procedure in selected cases, however, additional surgery should be considered if pathologic result is corresponding to intermediate or high risk group.
Prevalence of historical medical conditions or comorbidities with potential role in clinical decision making related to suitability of immuno-oncologic plus IV antiangiogenic therapy in newly diagnosed first-line unresectable hepatocellular carcinoma in the United States.
Authors: Tammy Schuler, Leonardo Passos Chaves, Shital Kamble, Emily Bland, Bruce A. Feinberg
Journal: Journal of Clinical Oncology (2023)

511 Background: Treatment landscape in advanced/unresectable hepatocellular carcinoma (uHCC) has been rapidly changing. In June 2020, the first immuno-oncologic (I/O) + IV anti-angiogenic regimen for uHCC was approved as first line (1L) treatment in the US. As with any new therapy, it is key to understand the prevalence of medical conditions listed in patient medical history/comorbidities that could potentially influence physician choice of 1L therapy in uHCC patients. Methods: We conducted a retrospective chart review study using Cardinal Health's Oncology Provider Extended Network (OPEN). US medical oncologists identified newly diagnosed adult uHCC patients initiating 1L systemic therapy from June 2020 to April 2022. Based on the warnings and precautions section of the US FDA labels, medical conditions reported as part of patient medical history or comorbidities [including gastrointestinal (GI) bleeding risk, chronic kidney disease, autoimmune disorders, thromboembolic events] were identified from patient medical records. Less suitable was defined as the occurrence of ≥ 1 medical condition/comorbidity reported in the medical record. All patient data were deidentified. Proportions of patients with the above medical conditions or with physician-reported record of an esophagogastroduodenoscopy (EGD) procedure to assess risk of bleeding were calculated. Results: In the cohort of 433 uHCC patients initiating 1L systemic therapy, majority were male 287 (66%), Caucasian 244 (56%) with average age of 64 years. At 1L initiation, majority of the patients were 333 BCLC Stage C (77%) and 316 (73%) had ECOG performance status of 0 or 1. Approximately 160 (37%) were Child-Pugh B, 99 (23%) had non-alcoholic steatohepatitis (NASH), 176 (41%) had Hep-C etiology (among those tested), and 294 (68%) had liver cirrhosis. Prior to therapy initiation, 254 (59%) received EGD within 3 months. In the overall cohort, 221 (51%) patients were reported to have at least one condition listed as medical history/comorbidity that could make them less suitable to receive I/O + IV anti-angiogenic regimen. Upper/lower GI bleeding risk and chronic kidney disease were reported in 164 (38%) and 64 (15%) patients, respectively. History of thromboembolic events and autoimmune disorders were reported in 50 (12%) and 22 (5%) of patients, respectively. Conclusions: A significant proportion of the newly diagnosed uHCC patients were found to have at least one condition listed as medical history/comorbidity that would make them potentially less suitable for I/O + IV anti-angiogenic regimen. Our findings reinforce the importance of medical history and co-morbidity assessment in uHCC patients prior to therapy selection to optimize benefit-risk ratio for each patient.
Adjuvant chemotherapy for resected intrahepatic cholangiocarcinoma confers no survival advantage.
Authors: Jeremy Sharib, Annie Liu, Sarah Margaret Helena McIntyre, Kristen Elizabeth Rhodin, Nancy E. Kemeny, Andrea Cercek, James J. Harding, Ghassan K. Abou-Alfa, Kevin Soares, Alice Chia-chi Wei, Jeffrey A. Drebin, T. Peter Kingham, Michael Ian D'Angelica, Hope Elizabeth Uronis, John H Strickler, Michael Morse, Sabino Zani, Peter J Allen, William R. Jarnagin, Michael Lidsky
Journal: Journal of Clinical Oncology (2023)

560 Background: Randomized data suggest improved survival with adjuvant chemotherapy for biliary tract cancers, but subset analyses of intrahepatic cholangiocarcinoma (ICC) show limited survival benefit. This study uses a large bi-institutional cohort of resected ICC patients to evaluate the impact of adjuvant therapy on recurrence patterns and overall survival (OS) and compares these findings to data from a national cancer registry. Methods: Patients with resected ICC were identified within a bi-institutional cohort (Duke and Memorial Sloan Kettering, 1997-2020) and the National Cancer Database (NCDB, 2010-2018). Patients were stratified by treatment with adjuvant chemotherapy (adj). Site of first recurrence was categorized as local (liver only), regional (liver and perihepatic nodes), nodal (perihepatic nodes only), distant, or mixed (both liver and distant). OS was compared with Kaplan-Meier methods. Results: 367 patients underwent resection for ICC, and 163 (44%) patients received adjuvant therapy. Median follow-up was 33 vs. 44 months (adj vs observation (obs), p=0.15). 263 (72%) patients had recurrent disease, most commonly in the liver (72%). There was no difference in recurrence patterns stratified by treatment with adjuvant chemotherapy (% recurrence, adj vs obs; local: 42 vs 42; regional: 2 vs 2; nodal: 0 vs 3; distant only: 27 vs 26; mixed: 29 vs 27, p=0.5). OS was the same between groups (adj vs obs; 42 vs 49 months, p=0.3) and when stratified by recurrence site (p=0.5). Similarly, in an NCDB cohort of 1,159 ICC patients over the same time period, there was no association between adjuvant therapy and OS (adj vs obs; 49 vs 57 months, p=0.1). Conclusions: In this retrospective dual registry analysis, corroborated by national data, adjuvant chemotherapy was not associated with an improvement in OS in ICC patients subjected to curative intent resection. Further, adjuvant therapy had no impact on the high rate of hepatic recurrence, suggesting that alternative strategies, such as liver directed therapies, are needed to improve recurrence rates and OS.
Impact of obesity on postoperative outcomes in patients undergoing esophagectomy for resectable esophageal cancer.
Authors: Nikhil Patel, Pranav Patel, Joseph Doyle, Georgios Geropoulos, Ricky Harminder Bhogal, William H. Allum, M. Asif Chaudry, Sacheen Kumar
Journal: Journal of Clinical Oncology (2023)

327 Background: The prevalence of obesity (Body Mass Index&gt;30kg/m^2) is rising in the western world and is a risk factor for gastrointestinal malignancy. It is considered a risk factor for poor surgical outcomes including impaired wound healing and venous thromboembolism. Dysphagia is a late sign of esophageal cancer and is associated with pre-operative malnutrition and weight loss. However, the true impact of obesity on outcomes after esophagectomy is controversial. This analysis investigates the impact of pre-operative obesity on outcomes following esophagectomy for esophageal cancer. Methods: All patients with recorded pre-treatment BMI, who underwent surgery from January 2005 to June 2022 at a single tertiary, specialist cancer centre in the United Kingdom (UK), were included in this study. Demographic details including BMI and tumour staging (TNM classification) were collected, as well as total length of inpatient and critical care admission (LOS), 30- and 90- day mortality. Statistical analyses were performed on the R platform. Results: A total of 401 patients (348 male, 53 female) underwent resectional surgery for esophageal cancer; 132 (32.9%) were of normal BMI (18.5-24.9kg/m^2), 162 (40.1%) were overweight (BMI of 25-29.9kg/m^2), and 108 (26.9%) were obese (BMI&gt;30kg/m^2). The mean BMI for obese patients was 33.6kg/m^2 and mean age was 62.5 years in this cohort. Laparoscopic Ivor-Lewis esophagectomy was the commonest procedure performed on obese patients (57/108, 52.3%). When all patients were categorised into healthy BMI, overweight or obese cohorts, there was no statistically significant difference in post-operative complications at Clavien-Dindo grade II or lower, (p=0.500) or grade IIIa or higher (p=0.201). Furthermore, there was no statistically significant difference in total inpatient LOS (p=0.503), length of critical care admission (p=0.358), 30-day (p=0.836) or 90-day mortality (p=0.691). Conclusions: Obesity is not significantly associated with increased risk of postoperative complications, LOS, 30- or 90-day mortality in patients undergoing esophagectomy for cancer. The increasing uptake of minimally invasive surgery for esophageal cancer resections may also be associated with favourable surgical outcomes being achieved in patients with BMI&gt;30kg/m^2.
Plasma-only multiomic minimal residual disease (MRD) testing in 2,000 consecutive patients with colorectal cancer (CRC).
Authors: Katrina Sophia Pedersen, Benjamin R. Tan, Xiaotong Zuo, Lesli A. Kiedrowski, Leslie Bucheit
Journal: Journal of Clinical Oncology (2023)

28 Background: Use and impact of circulating tumor DNA (ctDNA) testing for MRD detection has been infrequently reported outside clinical trials. We report clinical use of a validated plasma-only multi-omic MRD assay in a large, unselected CRC cohort, including clinically annotated cases. Methods: The first 2,000 US patients (pts) with documented stage (stg) and Guardant Reveal MRD test results since clinical launch in Feb 2021 were queried; all tests per pt were analyzed (data cut-off: July 2022). Pts could be enrolled in a post-operative program (POP, up to 3 tests 3-16 weeks post-resection) or a surveillance program (SP, after treatment) for recurrent tests; pts could also have one-time tests. Programs were analyzed for stg II/III only. Clinical factors were extracted from test requisition forms; pts from Siteman Cancer Center had additional data extracted from medical records. Results: 1994 pts met criteria for analysis with median age of 64 (range 21-95); 1,112 (56%) were male. ctDNA was detected in 27%, with detection increasing by stg (Table). 30% of positive samples were detected by methylation only, a 43% increased detection over genomic only analysis. 505/544 positive pts had &gt;1 test: 20% had ctDNA first detected on a subsequent test, a 25% increase when testing serially. Most stg II/III pts were tested in the SP. Stg II pts tested POP had a median turnaround time of 10 days (range 6-42); 96% had results prior to 12 weeks post-resection. In the annotated subgroup of 28 pts (65 tests), 8/28 (28%) had ctDNA detected. 13 pts had rectal- and 15 had colon cancer. 11/28 (39%) were stg II, 13 (46%) stg III, 4 (14%) stg IV. 26/28 had surgery, 7/13 rectal pts had neoadjuvant chemotherapy and/or radiation prior to ctDNA testing. 8 (29%) pts recurred. At data cut-off, assay sensitivity to predict or confirm recurrence was 80% (95%CI: 44.4-97.5%), specificity 100% (95%CI: 81.5-100%), PPV 100%, NPV 90% (95%CI:72.26-96.9%). Two pts with recurrence and negative ctDNA had their last test &gt;6 months prior to recurrence. Testing informed clinical decision-making in 11 (39%) pts to proceed with systemic therapy (5), repeat scans sooner (2), proceed with biopsy (1), or confirm recurrence (3). Conclusions: Through real-word data, we confirm prior studies showing multi-omic plasma-only MRD testing has high sensitivity and specificity for recurrence and now show use of the assay in clinical decision-making. Notably, methylation analysis and serial testing both improved detection of MRD and impacted clinical care. These findings should continue to be studied in larger cohorts and randomized trials. [Table: see text]